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European Journal of Gastroenterology & Hepatology | 2006

Serum levels of hepatoprotective peptide adiponectin in non-alcoholic fatty liver disease.

Cem Aygun; Omer Senturk; Saadettin Hulagu; Suleyman Uraz; Altay Celebi; Tolga Konduk; Birsen Mutlu; Zeynep Cantürk

Objective Adiponectin is an adipose tissue-specific protein that has anti-inflammatory, antidiabetic and antiobesity effects. It has been suggested that adiponectin has a hepatoprotective role. Non-alcoholic fatty liver disease (NAFLD) is becoming more prevalent with increasingly adverse clinical outcomes. In this study, serum adiponectin levels were investigated in patients with NAFLD to determine its possible role on hepatic inflammation and injury. Methods Twenty-nine biopsy-proven NAFLD patients (14 women, 15 men) with elevated liver enzymes, 20 clinically diagnosed NAFLD patients (13 women, seven men) with normal liver enzymes, and 20 healthy adults (10 women, 10 men) were enrolled. From fasting blood samples, serum adiponectin levels were measured by enzyme-linked immunosorbent assay. The body mass index, serum glucose, insulin, cholesterol and triglyceride levels were determined. Results Serum adiponectin levels were 4.99±2.1, 9.49±3.91 and 7.74±4.41 μ/ml in the NAFLD with elevated liver enzymes, NAFLD with normal liver enzymes and healthy adult control groups, respectively. The mean serum adiponectin level in the NAFLD with elevated liver enzymes group was significantly lower than those of other groups tested (P<0.001). Insulin, cholesterol and triglyceride levels of NAFLD patients with elevated liver enzymes were significantly higher than control groups (P<0.05) but were not significantly different from the NAFLD group with normal liver enzymes (P>0.05). On histopathologic examination, the mean serum adiponectin levels of non-alcoholic steatohepatitis patients with grade 2 or more inflammatory activity was significantly lower than patients with grade 1 inflammatory activity (P=0.013). Conclusion Serum adiponectin levels are significantly lower in NAFLD patients with elevated liver enzymes. Non-alcoholic steatohepatitis patients show lower levels of adiponectin with higher grades of inflammation.


Digestive Diseases and Sciences | 2008

Association of apolipoprotein E polymorphisms in patients with non-alcoholic steatohepatitis.

Ali Sazci; Gurler Akpinar; Cem Aygun; Emel Ergul; Omer Senturk; Sadettin Hulagu

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal hepatic steatosis in the absence of alcohol abuse worldwide. Non-alcoholic steatohepatitis (NASH) is the most progressive form of NAFLD. The aim of this study was to investigate the role of apolipoprotein E (APOE) polymorphisms in the development of NASH. We analysed 57 NASH patients and 245 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a case–control study. The diagnosis of the patients was based on liver biopsy. The serum levels of glucose, lipids, vitamin B12, folic acid, homocysteine, insulin, total biluribin, total protein, albumin, ferritin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined in all of the subjects. Body mass index (BMI), waist circumference (WC), AST, ALT, fasting blood sugar (FBS), total cholesterol, triglyceride (TG), low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, insulin and ferritin levels were significantly higher in the 57 patients with NASH compared with the 245 healthy controls. The APOE ε3 allele was overrepresented in the whole group of NASH patients (ε3=97.37% in NASH versus 82.45% in controls). The APOE polymorphism was statistically significantly associated with NASH (χ2=15.741; p=0.008). The APOE3/3 genotype (odds ratio [OR]=7.941; p=0.000) was strongly associated with increased risk for NASH in all NASH patients. Consequently, the APOE3/3 genotype may play a role in the aetiopathogenesis of NASH.


Endocrine Research | 2001

PREVALENCE AND COMPARISONS OF FIVE DIFFERENT DIAGNOSTIC METHODS FOR HELICOBACTER PYLORI IN DIABETIC PATIENTS

Omer Senturk; Zeynep Cantürk; Berrin Cetinarslan; Cengiz Erçin; Sadettin Hulagu; Nuh Zafer Cantürk

Helicobacter pylori is now regarded as a major gastroduodenal pathogen that is etiologically linked with duodenal and gastric disease. It has been suggested recently as an important factor for nongastroenterologic conditions such as coronary heart disease and diabetes mellitus. In this study, we planned to investigate the prevalence of H. pylori in diabetic patients and to evaluate five different diagnostic tests. Group I consisted of 67 patients with type II diabetes mellitus and seventy-three aged-matched health people served as control in group II. Group I was divided in two subgroups with good (Group IA) and poor (Group IB) glycemic control. H. pylori was diagnosed by five different tests: 1) biopsy, 2) culture, 3) gram staining, 4) imprint cytology and 5) brushing cytology. The usefulness of each test for each group was statistically compared. There was a higher prevalence for H. pylori in diabetic patients. This study showed that two positive out of five tests was most reliable for predicting the H. pylori in diabetic and nondiabetic patients. In conclusion, the prevalence of H. pylori is high in diabetic patients. Peristaltic activity, and impaired nonspecific immunity must be evaluated as risk factors in diabetics. We recommend that the ‘gold standard’ should be regarded as two positive out of these five different tests.


European Journal of Internal Medicine | 2008

Echinacea-induced severe acute hepatitis with features of cholestatic autoimmune hepatitis.

Orhan Kocaman; Sadettin Hulagu; Omer Senturk

The use of herbal drugs has been increasing in all countries in recent years. Preparations made from plants of the genus Echinacea are widely used for the prevention and treatment of colds [1]. Hepatotoxicity related to phytomedicine requires a high level of suspicion, and the diagnosis is often delayed in clinical practice. There are no reports describing acute cholestatic autoimmune hepatitis (ACAH) induced by Echinacea in the medical literature. We herein report the case of a patient with ACAH due to Echinacea. A 45-year-old male patient was admitted to our hospital complaining of fatigue and jaundice of 1-week duration. The patient had caught a cold one month before admission. In spite of the disappearance of common cold symptoms within one week, fatigue and jaundice appeared one week before hospitalization. The patient denied use of medication in the initial history-taking; however, 3 days after he was admitted, he told us that he had started taking Echinacea (Echinacea root tb; 1500 mg/day) after catching the cold the previous month in order to strengthen his immune system. Physical examination revealed an icteric patient. Initial laboratory evaluation on admission showed a sedimentation rate of 54 mm/h, alanine aminotransferase 1260 IU/L (normal: b55 IU/L), aspartate aminotransferase 840 IU/L (normal: b34 IU/L), alkaline phosphatase 984 IU/L (normal: b150 IU/ L), gammaglutamyl transferase 672 IU/L (normal: b64 IU/L), total bilirubin 2.8 mg/dL (normal: b1 mg/dL), direct bilirubin 1.9 mg/dL (normal: b0.5 mg/dL), albumin 3.3 g/dL (normal: 3.5–5 g/dL), gamma globulin 5.2 g/dL (normal: 1.1–3.5 g/ dL), prothrombin time 19.2 s (normal: 12–15.5 s), and INR 1.3. The concentration of immunoglobulin G (IgG) was 2240mg/dL (normal: 751–1560mg/dL). Anti-smooth muscle antibodies (SMAs) were positive (titer 1:80). Anti-nuclear antibodies, anti-liver/kidney microsomes, anti-soluble liver antigen antibodies, and anti-mitochondrial antibodies were negative. Markers for viral hepatitis, ceruloplasmin, iron and ferritin levels, and alpha 1 antitrypsin level were not remarkable for acute hepatitis. Liver biopsy revealed interface hepatitis, prominent cholestasis, and portal lymphoplasmocytic and eosinophilic granulocyte infiltration. After admission, the patient stopped taking theEchinacea. By follow-up, the transaminases and cholestatic enzymes had spontaneously decreased. One month later, all laboratory values were normalized, except for SMA positivity. The presence of highly elevated liver enzymes, positive IgG and SMAs, and spontaneous normalization of laboratory values after dechallenge with Echinacea fit the diagnosis of Echinacea-induced ACAH. This is the first report of Echinacea-induced ACAH. Echinacea, with its effect of increasing the number and activity of immune system cells [2], may result in a breakdown of autoimmunity self-control in the liver, which may present with ACAH, in susceptible patients.


Inflammatory Bowel Diseases | 2006

Endothelial dysfunction in patients with ulcerative colitis.

Orhan Kocaman; Tayfun Sahin; Cem Aygun; Omer Senturk; Sadettin Hulagu

Background: Human intestinal microvessels from chronically inflamed ulcerative colitis (UC) show microvascular endothelial dysfunction. Whether generalized endothelial dysfunction could associate with UC has not been explored yet. Our aim was to assess the endothelial function in the patients with different UC activity and to hypothesize about the relationship of endothelial function to activity‐related extraintestinal complications (AREC) of UC. Methods: Twelve patients with mild UC, 14 patients with moderate UC, 16 patients with severe UC, and 24 healthy subjects were included in the study. The activity of UC is calculated according to the Seo Index. Endothelial functions of the brachial artery were evaluated by using high‐resolution vascular ultrasound. Endothelial‐dependent dilatation (EDD) was assessed by establishing reactive hyperemia and endothelial‐independent dilatation (EID) was determined by using sublingual isosorbide dinitrate. Results: EDD was significantly worse in patients with severe UC as compared with patients with mild UC (8.7 ± 1.6% versus 17.3 ± 5.6%, P < 0.05) and even in patients with moderate UC as compared with patients with mild UC (13.1 ± 3.2% versus 17.3 ± 5.6%, P < 0.05). EDD was not significantly worse in patients with mild UC as compared with healthy subjects (17.3 ± 5.6% versus 18.1 ± 8.1%, P > 0.05). EID was significantly worse in patients with severe UC compared with patients with moderate UC (10.5 ± 2.9% versus 13.4 ± 3.7%, P < 0.05) and even in patients with mild UC compared with healthy subjects (20 ± 6.7% versus 31.1 ± 12.6%, P < 0.05). EDD and EID were significantly worse in patients with AREC compared with patients with no AREC (9.5 ± 2.5% versus 14.9 ± 5.1%, P < 0.05; 11.6 ± 4.3% versus 16 ± 6.1%, P < 0.05, respectively). Conclusions: Increased activity of UC is associated with significant endothelial dysfunction, which may relate to the pathophysiology of AREC of UC.


World Journal of Gastroenterology | 2011

Endoscopic submucosal dissection for premalignant lesions and noninvasive early gastrointestinal cancers.

Sadettin Hulagu; Omer Senturk; Cem Aygun; Orhan Kocaman; Altay Celebi; Tolga Konduk; Koç Dö; Goktug Sirin; Uğur Korkmaz; Ali Erkan Duman; Neslihan Bozkurt; Gökhan Dindar; Tan Attila; Yesim Gurbuz; Orhan Tarcin; Cem Kalayci

AIM To investigate the indication, feasibility, safety, and clinical utility of endoscopic submucosal dissection (ESD) in the management of various gastrointestinal pathologies. METHODS The medical records of 60 consecutive patients (34 female, 26 male) who underwent ESD at the gastroenterology department of Kocaeli University from 2006-2010 were examined. Patients selected for ESD had premalignant lesions or non-invasive early cancers of the gastrointestinal tract and had endoscopic and histological diagnoses. Early cancers were considered to be confined to the submucosa, with no lymph node involvement by means of computed tomography and endosonography. RESULTS Sixty ESD procedures were performed. The indications were epithelial lesions (n = 39) (33/39 adenoma with high grade dysplasia, 6/39 adenoma with low grade dysplasia), neuroendocrine tumor (n = 7), cancer (n = 7) (5/7 early colorectal cancer, 2/7 early gastric cancer), granular cell tumor (n = 3), gastrointestinal stromal tumor (n = 2), and leiomyoma (n = 2). En bloc and piecemeal resection rates were 91.6% (55/60) and 8.3% (5/60), respectively. Complete and incomplete resection rates were 96.6% (58/60) and 3.3% (2/60), respectively. Complications were major bleeding [n = 3 (5%)] and perforations [n = 5 (8.3%)] (4 colon, 1 stomach). Two patients with colonic perforations and two patients with submucosal lymphatic and microvasculature invasion (1 gastric carcinoid tumor, 1 colonic adenocarcinoma) were referred to surgery. During a mean follow-up of 12 mo, 1 patient with adenoma with high grade dysplasia underwent a second ESD procedure to resect a local recurrence. CONCLUSION ESD is a feasible and safe method for treatment of premalignant lesions and early malignant gastrointestinal epithelial and subepithelial lesions. Successful en bloc and complete resection of lesions yield high cure rates with low recurrence.


Indian Journal of Gastroenterology | 2013

Adalimumab-induced psoriasis in a patient with Crohn's disease.

Ugur Korkmaz; Ali Erkan Duman; Gökhan Dindar; Hasan Yilmaz; Ibrahim Hakki Dursun; Altay Celebi; Omer Senturk; Sadettin Hulagu

Sir: Inappropriate secretion of tumor necrosis factor alpha (TNF-α) leads to inflammation and tissue damage by causing excessive secretion of inflammatory cytokines especially IL-1 [1]. AntiTNF-α agents are used to treat a myriad of immune-based diseases. Although indicated in treating certain forms of psoriasis, TNF inhibitors have paradoxically been shown to cause or worsen psoriasis primarily in patients with underlying rheumatologic disease and inflammatory bowel diseases (IBD) [2, 3]. We present a case of plaque psoriasis in a patient with Crohn’s disease during adalimumab treatment. A 32-year-old female patient with the diagnosis of ileal Crohn’s disease for 5 years was started on adalimumab therapy (160 mg initially on day 1, followed by 80 mg on day 15, and a maintenance dose of 40 mg every other week) due to refractory disease. Following the loading dose, a marked improvement was seen in both clinical and laboratory indices (defined as a decrease in CDAI ≥100 points). In the fourth month of treatment, itchy irregular white desquamated plaques with surrounding hyperemia appeared on the extensor and partly flexor surfaces of the extremities and also on the scalp. Plaques with fissures were seen on the thenar parts of the hands (Fig. 1a, b). The patient was diagnosed with psoriasis. As psoriasis was believed to occur as a side effect of adalimumab, therapy was stopped and switched to methotrexate 15 mg/week plus infliximab 5 mg/kg/week in the 12th week of the treatment, laboratory findings were within normal range, and the patient suffered only from mild abdominal pain. Plaques were judged to show an improvement to a degree of approximately 90 % on the extremities and 50 % on the scalp. Treatment was maintained by adding topical therapies. Anti-TNF-α drugs play a key role in the treatment of IBD. Psoriasis is rarely seen in IBD patients using anti-TNF drugs and most of these cases are related to infliximab therapy [3–5]. The most common anti-TNF-α-related forms of psoriasis are plaque psoriasis and palmoplantar pustulosis [3, 5]. Signs occur after 1 to 96 months from the implementation of therapy [5]. Psoriasis development during anti-TNF-α therapy is believed to be a result of the disruption of the balance between TNF-α and interferon alpha [6]. Inhibition of TNF-α also leads to hyperproliferation of keratinocytes by decreasing levels of cytokines such as IL-6, IL-8, etc. [7]. Although there is no established treatment modality for such cases, stopping the offending drug provides a marked improvement. Switching to another drug from the same class, adding an immunomodulatory drug like methotrexate, and topical therapies (including vitamin D) are also recommended [3, 5, 6]. Although lesions might also heal during continuation of therapy, stopping the therapy yielded better responses [5]. In our case, both IBD and skin lesions (except scalp lesions) could be treated by stopping the offending drug and starting methotrexate along with infliximab (as Crohn’s disease was unresponsive to previous immunomodulatory therapies). Vitamin Dwhich has immunomodulatory effects (especially in plaque psoriasis) permits to lower the doses of other drugs used for the treatment of psoriasis [8]. Healing of plaques by vitamin D replacement is reported in adalimumab-induced psoriasis [9]. As skin lesions seen in IBD might be a manifestation of the disease, it should be always kept in mind that they might be the side effect of the drugs used for the treatment of the disease. U. Korkmaz (*) :A. E. Duman :G. Dindar :H. Yilmaz : A. Celebi :O. Senturk : S. Hulagu Department of Gastroenterology, Kocaeli University Medical Faculty, Umuttepe, 41900 Kocaeli, Turkey e-mail: [email protected]


European Journal of Internal Medicine | 2009

Severe migraine attacks during treatment of chronic hepatitis C

Orhan Kocaman; Gulsen Kocaman; Omer Senturk

Migraine is a benign disorder with recurrent attacks of disabling headache. The diagnosis is made according to the criteria proposed by the International Headache Society (IHS) [1]. Anemia is a common finding during the treatment of chronic hepatitis C virus (HCV) infection. Anemia induced cranial ischemia and increased prostaglandin E2 levels during the treatment of HCV infection may cause migraine attacks in genetic susceptible patients [2]. Migraine attacks during HCV treatment may result in poor treatment compliance with reduced success rate of HCV treatment. A 38-year-old male patient with chronic HCV infection was admitted to our department. In laboratory investigation, ALTand HCV RNA were found 118IU/L (normal: b 55IU/L) and 1,350,000IU/mL, respectively. Liver biopsy showed chronic hepatitis with severe fibrosis. Pegylated interferon (Peg-IFN) and ribavirin were started. At 12 weeks of treatment, a throbbing headache with nausea, vomiting and oversensitivity to light and sound was emerged. He was diagnosed with migraine according to the criteria of the IHS [1]. The complete blood count revealed hemoglobin 9.2 g/dL and hematocrit 28%. Treatment with 1U of erythrocyte transfusion and nonsteroidal antiinflammatory drug resulted in remission of migraine attack. Ribavirin (1000 mg/ day) was continued without any change in the dose after attack. 12 days later, he experienced a second migraine attack with the laboratory findings of hemoglobin 9 g/dL and hematocrit 26.4%. The migraine attack subsided after hemoglobin level was elevated to 9.8 g/dL with 1 U of erythrocyte transfusion. Following the second attack, he was given only peg-IFN and experienced no migraine attack for 15 days. At the end of the follow up, hemoglobin and hematocrit were found to be 10.2 g/ dL and 31%, respectively. Ribavirin-related anemia was thought


The American Journal of Gastroenterology | 2001

Postcholecystectomy microscopic colitis: Is bile acid malabsorption a triggering factor?

Yesim Gurbuz; Omer Senturk; Bahar Muezzinoglu

Abdominal and pelvic CT scans were without abnormalities. Her medications included omeprazole for 4 yr and self-prescribed mahuang for 4.5 months for weight loss. She denied tobacco use, alcohol consumption, ill contacts, and recent travel. The physical examination revealed stable vital signs, obesity, jaundice, scleral icterus, and a benign abdomen. Upon hospitalization laboratory studies revealed a normal complete blood count, AST 671 mg/dl, ALT 293 mg/dl, alkaline phosphatase 320 mg/dl, bilirubin 9.3, and prothrombin time 21.1. Abdominal ultrasonography showed diffuse hepatocellular disease and ascites. A liver biopsy revealed severe inflammatory activity, predominant polymorphonuclear neutrophils, moderate fibrosis, and lobular necrosis. Subsequent tests were notable for a positive antismooth muscle antibody 1:320 and a negative fluorescent antinuclear antibody. She was started on steroids, but encephalopathy developed and she was transferred to a liver transplant center. While she awaited transplantation, her status gradually improved and she was discharged in stable condition. The best known adverse effects of ma huang are palpitations, nervousness, headache, and insomnia. However, there are limited data about the hepatotoxic effects of ma huang. Review of the literature reveals one reported case of ma huang associated with acute hepatitis that gradually resolved after discontinuation (6). It is possible that our patient had an immune-mediated mechanism of liver injury. This may be supported by the positive anti–smooth muscle antibody and eosinophils present on liver biopsy. It is also possible that our patient had subclinical autoimmune hepatitis that was exacerbated by the self-prescribed ma huang. If subclinical autoimmune hepatitis was present, it is possible that an exacerbation would have occurred without ma huang consumption. However, the temporal relationship between ma huang use and the fulminant hepatitis implicates ma huang as a potential cause of the hepatitis. It is important for clinicians to recognize the widespread use of alternative therapies. The potential hepatotoxic effects of ma huang need to be further evaluated.


The Turkish journal of gastroenterology | 2018

Differential diagnosis of Crohn’s disease using antibodies to glycoprotein 2 and Saccharomyces cerevisiae

Ali Erkan Duman; Sadettin Hulagu; Altay Celebi; Uğur Korkmaz; Mahmut Mert Musul; Omer Senturk; Goktug Sirin; Hasan Yilmaz; Koç Dö; Gökhan Dindar; murat öztürkler; Neslihan Bozkurt; Hale Maral Kir

BACKGROUND/AIMS Glycoprotein 2 (GP2), the major autoantigen of Crohns disease (CD)-specific pancreatic autoantibodies, is reportedly correlated with several characteristics of CD. We investigated this serological marker in Turkish patients with CD and assessed its utility in combination with anti-Saccharomyces cerevisiae antibodies (ASCAs) for differential diagnosis of CD. MATERIALS AND METHODS A total of 60 patients with CD, 62 patients with ulcerative colitis (UC), and 46 healthy controls with a definite diagnosis who were similar in age and sex were enrolled in the study conducted from November 2011 to October 2012. ASCA and anti-GP2 levels were measured using commercially available kits. RESULTS Anti-GP2 IgA and IgG levels were higher in patients with CD (25%) than in those with UC (5%) and controls (2%). The seroprevalence of anti-GP2 IgA was markedly higher than that of IgG in patients with CD in contrast to previous studies. The specificity and positive predictive value of seropositivity for both ASCA and anti-GP2 were 100%. ASCA IgA seropositivity was correlated with a complicated disease course and a history of surgery. There was no correlation between anti-GP2 seropositivity and disease location, disease behavior, or a history of surgery. CONCLUSION The combination of ASCA and anti-GP2 may enable differentiation of CD from UC. As ASCA seropositivity is associated with a more complicated disease course, patients seropositive for ASCA at the initial diagnosis should undergo more intense therapy.

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Uğur Korkmaz

Abant Izzet Baysal University

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